Triazeve pharmaceuticals



Unitfid States Patent TRIAZINE PHARMACEUTICALS Jack Bernstein, New Bruuswick,.and Ervin R. Spitzmiller,

fli'gliland Park, N. J., assignors to ,Qlin Mathieson chemijcal' Corporation, New York; N. Y., a corporationofvirg'iuia' No Drawing; Application July 20,1953, Serial No.- 3695246 wherein R" and R! are each aikyl (preferably'lowe'f alkyr or, together with the N atom to which they'ar'e joined, form a heter'ocyclic' ring';.R"' is alkyl or ara1kyl; xis' a pharmacologically acceptable anion; Y is O, S, NH 01' N-lbwer alk'yl (preferably Z ishydrogen or R" x R, R" and Xhaving the same meanings as given above; and n'is an integer from I to 7, both inclusive. Thus, R; R' andR maybe alkylg-roups, such-as methyl,- ethyl;.propyl, isopropyl, butyl, sec. butyl,. amyl, hexyl, ethyl-hexyl,.dodecyl and octadecyl. Also R-and R may be combined with the-N atom towhich they are joined to-fornra heterocyclic group, such aspiperidine; mor-' pholine, and py'rrolidine; andR- may be aralkyl, such asbenzyl,-p.-nitrobenzyl, m-ehlorbenzyl, phenethyl, p-nitro phenethyl, p-brornphenethyl, phenylisopropyl, p-nitr'ophenylis'opropyl; p.-chlorophenylisopropyl and naphthyl methyl. The pharmacologically-acceptableanionmay be a-nhalogen, such as-chlorine, bromine, or"'iodine;'-or any other anion, such as sulfate, methosulfate, tartrate, citrate-,- phosphate or acetate. Preferred are the tri-ether quaternaries in which R and R are lower alkyl, R" is benzyl, n is 2=andX is'halogen.

Thus, specifically included among the compounds'of this invention aresuch quaternary ammonium salts as: 1,3,5-

triazino 2,4,6 tris(oxyethyleneytris trimethyl-ammonium- 2,725,379 Patented Nov. 29, 1955 11m iodide. Also specifically included are such tertiary amines asz' 1,3,5-triazino-2,4,6-tris(oxypropylene)-tris-di 'thylamine; 1,3,5-triazino-2,4,6-tris(oxyethylene)-tris-dieth'ylamine; 1,3,5 triazino 2,4,6 tris(oxyisopropylene)- tris-dipropylamine; 1,3,5-triazino-2,4,6-tris(oxyethylene) t'ris-methyl-ethylamine; 2,4,6-tris-N-oxyethylmorpholino- 1,3,5-tr'iazine; 2,4,6 tris N oxyethylpiperidino-1,3,S-triazi'ne; and 2,4,6 tris(ti-diethylaminoisopropylmercapto)- l,-3,5'-triazine'. The acid-addition salt form of these ether and thioether amino compounds is, of course, within the purview of the invention, the salts being those of either inorganic or organic acids (e. g. hydrochloric, sulfuric, phosphoric, thiocyanic, acetic, trichloracetic, citric, and tartaric).

Those compounds in which Y is oxygen (or sulfur) may be prepared by heating a cyanuric halide with analcoholate (or thioalcoholate) of a tertiary aminoalkanol (or atertiary aminoalkanthiol'), then treating the tertiary amine-containing ether (or thioether) thus formed with an inorganic acid ester to form the quaternary ammonium salt. Those compounds in which Y is NH or N-lower alkyl may be prepared by heating the cyanur'ic chloride directly with the desired tertiary aminoalkylamine, then quaternizing by treatment with an inorganic acid ester. Anhydrous conditions are preferably employed in the reactions-to prevent losses due to hydrolysis and other dc' composition.

The alcoholates (or thioalcoholates) used are prefer ablythose of the alkali or alkaline earth group (especial ly sodium); and the cyanuric halide is preferably in the form of the chloride.

Quaternary ammonium salts may also be formed by preparing the quaternary ammonium hydroxide (as [1'] by treating the quaternary ammonium iodide in aqueous solution with an excess of moist silver oxide and evaporatii'ig the filteredsolution-invaeuo or [21 by treating the quaternary ammonium chloride with potassium hydroxiide' in methanol, removing the potassium chloridewhich precipitates and evaporating the methanol from the re suiting solution), then treating the hydroxide with the desired a'cid (e. g. tartaric, citric, thiocyanic, phosphoric, are).

Acid addition salts of the tertiary amines may be pre pared either 'in aqueous solution or under anhydrous'con ditioifs for" example, by passing hydrogen chloride gas into an etherialsolution of the amine.

The cdmpounds may be administered intravenously, in isotoniesodium chloride solution, for muscle relaxation; and such-solution' may'include a small amount (of the order 'cf 0.25-1.0%) of a preservative, such as phenol befizyl-aleohol, chlorbutanol and sodium metabisulfitf For prolonged action, the compounds maybe formulated as a 's'u's'pens'ion in oil (e. g. peanut oil) containing added myricin. For example, such composition may contain about- 20 to40 mg. (preferably 30 mg.) agent and about 3510 m'g.;(preferably 50 mg.) myricin suspended in the-'peanutoil:

Following are specific working examples, illustrating but by no' means limiting the scope of this invention:

EXAMPLE I Preparation 0] 1,3,5-triazin0-2,4,6-tfis(oxyethylne) tris-triethyl-ammonium bromide mohohydrate (it) 2,4,6- tris(diethylamin0ethoxy)-1,3,5 triazine. In a'2-liter, S-necked flask equipped with a bulb reflux condenser and sealed stirrer, 23 g. metallic sodiumis added in small increments to 300 g. diethylaminoethanol, while maintaining anhydrous conditions. After the addition iscomplete (during which time the temperature rises to '.70-80- C.), the mixture is stirred for 4 hours; then allowed to remain overnight at room temperature. The undissolved sodium is removed from the reaction vessel and 58 g. cyanuric chloride, dissolved in 300 ml. anhydrous benzene, is added dropwise with stirring over a period of about 2.5 hours. The resulting reaction mixture is stirred at 75-80 C. for 8 additional hours, cooled to room temperature, then poured into 300 ml. cold water. The resulting mixture is transferred to 'a separatory funnel, and the benzene layer is separated, washed with saturated sodium chloride solution, then dried over anhydrous potassium carbonate and filtered. The benzene is removed by distillation at atmospheric pressure, and the unreacted diethylaminoethanol is separated by vacuum distillation; The remaining oil is then distilled in vacuo at 0.3 to 0.5 mm. Hg; and 59 g. product, distilling at l90-2l0 C., is separated. On redistillation, about 45 g. purified 2,4,6-tris(diethylaminoethoxy)-l,3,5- triazine [B. P. 178-182 C. at 0.2 to 0.3 mm. Hg] is obtained.

(b) 1,3,5 triazino 2,4,6 tris(oxyethylene) tris triethylammonium bromide m0n0hydrate.A 22 g. portion melting at 203-204 C. (dec.). On recrystallization from ethanol-hexane, purified l,3,5-triazino-2,4,6-tris(oxyethylene)-tris-triethylammonium bromide monohydrate is obtained, M. P. 207-208 C. (dec.). Pistol-drying over phosphorous pentoxide at 78 C. yields the anhydrous salt, M. P. 266-267 C.

EXAMPLE II Preparation of 1,3,5-triazin0-2,4,6-tris(aminoethylene)- tris-triethylammonium bromide (a) 2,4,6 tris(diethylaminoethylamine) 1,3,5 triazine.-In a 3-liter, 3-necked flask equipped with a bulb reflux condenser and sealed stirrer, 74 g. cyanuric chloride is added in small increments to 370 g. freshly distilled diethylaminoethylamine. Vigorous stirring is maintained during the addition as the temperature rises from 25 to 50 C. The temperature is then raised to about 80 C. and vigorous stirring is continued until a test for ionic chlorine indicates substantially complete reaction. The reaction mixture is then cooled to C. and 1 liter 5% aqueous sodium hydroxide is added. The resulting mixture is transferred to a separatory funnel and the aqueous layer is extracted several times with benzene after removing the organic layer. The benzene extracts are combined with the organic layer and the resulting solution is washed with saturated sodium chloride solution, dried over anhydrous potassium carbonate, and filtered. The benzene and diethylaminoethylamine are separated by in vacuo distillation and the residue is vacuum distilled to yield about 124 g. pure 2,4,6-tris(diethylaminoethylamine)-l,3,5-triazine, B. P. 216-218 C. at 0.1 mm. Hg.

(b) 1,3,5 triazino 2,4,6 tris(aminoethylene) tristriethylammonium br0mide.A 20 g. portion of the product obtained as described in (a) is dissolved in 150 ml. benzyl alcohol, added to 24 g. ethyl bromide, and the mixture is allowed to remain at room temperature for 48 hours in a stoppered flask. The benzyl alcohol is separated by distillation under high vacuum on a steam bath and the syrupy residue is triturated with an anhydrous mixture of acetone and ether. The amorphous precipitate which forms is separated by filtration and washed with anhydrous ether. On drying in a vacuum desiccator over phosphorous pentoxide, about 10 g. 1,3,5- triazino-2,4,6-tris (aminoethylene)-tris-triethylammonium bromide is obtained as a white solid, M. P. 235-238 C. (dec.). The product may be recrystallized from an ethanol-hexane mixture.

4 EXAMPLE III Preparation of 1,3,5triazino-2,4,6-tris(oxyethylene)-tri.rdiethylbenzylammonium chloride A 22 g. portion of 2,4,6-tris(diethylaminoethoxy)-1,3,5- triazine in 150 ml. benzyl alcohol is added to 28 g. benzyl chloride and the mixture is allowed to remain at room temperature for 96 hours under anhydrous conditions. The benzyl alcohol and excess ethyl bromide are separated by distillation under high vacuum on a steam bath and the oily residue is dissolved in chloroform, then recovered from the solution by adding anhydrous ether. On further trituration with anhydrous ether, the oil solidifies and is separated by filtration, yielding about 29 g. amorphous hygroscopic solid, M. P. -125 C. Recrystallization from ethylene dichloride, followed by desiccator drying under high vacuum over phosphorous pentoxide, yields the purified salt.

EXAMPLE IV Preparation of 1,3,5 triazino 2,4,6 lris(0xypr0pylene)- tris-triethylammoni-um bromide (a) 2,4,6 tris(diethylaminoprop0xy)-1,3,5-triazine.- In a 2-liter, 3-necked flask equipped with a bulb reflux condenser and sealed stirrer, 23 g. metallic sodium is added in small increments to 425 ml. freshly distilled gamma-diethylaminoprop anol, while maintaining anhydrous conditions. After the addition is complete (during which time the temperature is maintained at 60-70" C. by external heating), the temperature is raised to 80-90 C. and the mixture is stirred until solution of the sodium is complete." After cooling to room temperature, 61.5 g. cyanuric chloride dissolved in 400 ml. anhydrous benzene is added dropwise over a period of about 2 hours. The resulting mixture is then stirred at 75-80" C. for 5 hours, cooled to room temperature, then suction-filtered. The filtrate is concentrated by vacuum distillation and the oily residue is taken up in ether, washed with saturated sodium chloride solution, dried over anhydrous potassium carbonate, then filtered. The ether is separated from the filtrate by distillation and the remaining oil is distilled in vacuo at 0.1 to 0.3 mm. Hg to yield about 97 g. product distilling at 175-225 C. On redistillation, about 86 g. purified 2,4,6-tris(diethylaminopropoxy)-l,3,5-triazine is obtained (B. P. 196-200 C. at 0.1 mm. Hg).

(b) 1,3,5 triazine-2,4,6-tris(oxypropylene) tris-tri ethylammonium bromide.-A 23.5 g. portion of the prodnot obtained asdescribed in (a) is dissolvedin ml. benzyl alcohol added to 33 g. ethyl bromide, and the mixture is allowed to remain at room temperature for 60 hours in a stoppered flask. The benzyl alcohol and excess ethyl bromide are separated by distillation under-high vacuum on a steam bath; and the syrupy residue is triturated with anhydrous ether to yield, on filtratioman amorphous white solid which, when desiccator-dried over phosphorous pentoxide, yields about 27 g. product, M. P. 235-238 C. The product may be recrystallized from an ethanol-hexane mixture.

EXAMPLE -v I Preparation of 1,3,5 triazino tris 2,4,6(oxytrimth.-

ylene)-tris-diethylbenzyl ammonium chloride A 23.5 g. portion of the product obtainedas described in Example IV (a) is dissolved in 150 ml. benzyl alcohol,

added to 38.0 g. benzyl chloride, and the mixture is allowed to remain at room temperature for 60 hours in a stoppered flask. The benzyl alcohol and excess benzyl chloride are separated by distillation under high vacuum on a steam bath and the syrupy residue is triturated with a mixture of acetone and ether. The solvents are then decanted and the residue is taken up in anhydrous acetonitrile. Anhydrous ether is added to incipient turbidity and the mixture is then allowed'to remain at room temperature until crystallization is complete. pure product is recrystallized from a mixture of acetoni- This. irn

firmware trite-and anhydrous ether, then driedover remixingalco'- EXAMPLE VI Prepararionof 1,3,5 zriazinoi- 2,4,61- tris(oxyethylne)-' tris-trimethylammonium iodide:

(a) 2,4,6. tri.s'( 3'- dimethylaminoethoxy) 1,3,5-1riazine.ln a 3-liter, 3-necked.flask' equipped with a bulb reflux condenser and sealed stirrer, 23 g. sodium is added in small increments to 300' g; freshly distilled di'rnethylaminoeth'anol, while" maintaining anhydrous conditions. The mixture is allowed to'remain overnight at 'room't'em perature, then 62.0 g. cyanu'ric chloride dissolved in 500 ml. anhydrousb'enzene 'is added dropwise over a period of about 3'hou'rs; Vigorou'sistirring is maintained during the addition as the :temperatu're'risesto about60 C. The temperaturexis then raised to about 70-80 Cl and. vigorous-stirring is continued until "a test'for ionic chlorine indicates'substantially complete'reactio'n. The reaction mixture is then cooled to room temperature, filtered, and the filtrate concentrated by vacuum distillation. This crude product is taken up in'ether, washed with saturated sodium chloride solution, dried over anhydrous potassium carbonate,-then filtered, and the ether removed by distillation. Distillation under high vacuum yields'about 18 g. purified 2,4,6-tris(B-dimethylaminoethoxy)-1,3,5-tria.zine

(B. P. 158 C. at 0.4 mm. Hg);

(b) 1,3,5 trz'azino 2,4,6 tris(oxypropylene) tristriethylammonium iodidd -A 17 g. portion of the product obtained as described in (a) is dissolved in 200 ml. benzene ialcohol and'added to 42 g. methyl iodide in 100 ml. benzene-alcohol 'with stir ring'and cooling. The resulting mixture is: allowed toremain at room temperature for 8 days-intastoppered flask. A 100 mil portion of'anhydr'ous acetone is'then added and the precipitate which formsis separated .by' filtration, and dried ina vacuum-desiccator overtphosphorouspentoxide to yieldabout 32' g. 1,3;5- triazino-2,4,6-tris(oxypropylene)-tris triethylammonium iodide, M. P. 283-285 C. The iodide may be purified by recrystallization from anhydrous methanol to yield a product containing two mols' of methanol ofcrystallization.

EXAMPLE VII Preparation of 1,3,5 tr iazin-2,4,6-triswminoethylene) iris-diethylbenzylammonium chloride.

A21 g. portion of the product obtained: as described in Example Ilia) is dissolved in 150 m1. benz'yl alcohol, added to 18.9 g. benzyl chloride, .and the mixture is allowed to remain at room temperature for..96 hours in a stoppered flask. The benzyl alcohol is then separated by vacuum distillation and the syrupy'residue triturated with anhydrous ether. The crude product obtained on filtration is dissolved in tertiary butanol, then precipitated by adding anhydrous ether to the solution. The precipitate is .separated by. filtration, then dried in a vacuum desiccatorat 70 C(overphosphorous pentoxide to obtain the purified product.

EXAMPLE VIII Preparation of 1,3; triazino+2-meth0xy4,6-'bis(oxyefliyi ene),-bis-'diethylbenzyl ammonium'chloride" (a) 2-methoxy-4,6-bis(diethylaminoethoxy) ],3,5-tri azine:A solution of 70g; sodium alcoholate of .diethylaminoethanol in diethylaminoethanol (prepared'by di's solving 11.5-g. sodium in 200ml. diethylaminoethanol under anhydrous conditions) is added to asolution 0545' g'. 2,4dichloro-6 methoxyrs-triazine in 200 ml. benzene.

6. V unseen and the residue is '"purifid" by "fractionation" to yield-' about" 40 gr 2-meth0xy 4,6- bis(diethylaminoetlfoxy)-1,3,5-triazine, B. P. 157-160 C. at 0.5 mm. Hg.

(1;) 13,5 triazinm2-marhoxy-4;6 bis(oxyerhyl e)-bisdierhylb'enzyl ammonium chlorid.A solution of 25 g. benzyl 'chloride'in ml. anhydrousacetone is 'added'to 1 117 g. of "2 metlioxy 4;6=bis(diethylaminoethoxy) 1-l,'3,5= triazine andtheneaction mixture is allowed'towemainat room temperatme in"a stopperedflask until the'oil which gradually separates fromthe mixture crystallizes: The supernatant liquor is then decanted and the 'solid washed with ether; th'en tak'en up in chloroform. Acetone is 'acldcdto thechloroformsolution and theprecipitate which forms is =recrystallized- 'from chloroform and dried over phosphorous pentoxideto' yieldpure1;3,5 triazino 2 methoxy 4,6"- bi'stoxye'th'ylene) ;bis --dithy lhenzyl ammonium'chloride; P.- l43- l45 'C. (decz') with p eliminary softening." EXAMPILEIX' Preparation 1 of. 1,3,5-triazino.-2',4,6-tris[ t-aminoethylene- [3%(irinN methylmorpholino) J ammonium iodide,

(a) 2,4,6 tris N' omirmerhylfriorpholi'rw 1,3,6 ifl azine.-In a 3-liter, 3-necked flask equipped with a bulb reflux condenser and-seald' stirrer, a solution of 93 g. cyanuric chloride in 800 m1. benzene is added to a solution of496 g; N aminoethylmorpholine in 150 ml. benzene. The addition is'made dropwise'with stirring over a period of about 2 hours. The resultingmixture is then .warmed to gentle refiux"and"maintairied under these conditions until a'te'st for ionic. chlorine indicates substantially, come plete'reaction. Thereaction mixture isthencooled'to room"'t'emp,erature andfiltered, and-the filtrate is .transe frredto aseparatory'funnel, washed, first with 10% aqeuous sodium hydroxide, then with saturatedsodi'um chloride solution" and dried over anhydrous potassium carbonate; After filtration and removal'of the solvent by distillation; the solid 2,4,6-trisN-arninoethylmorpholine- 1,3',5-triazine is obtained.

(1)) 1,3,5'-triazino 2,4,6 tr'is[q amirioeth'ylene dtris-N methylmorpholino)] ammonium iodide.-'A 22.8 g:. portionof "the product obtained as described'in-v-(a) is dissolved in 100ml; anhydrous acetone, added to a solution' of.25. g; methyl iodide in 200 ml. acetone and -the mixture is 'allowed'toremain at room temperature in a stoppered flask until precipitation. is complete. Filtration yields about39 g. tan-colored hygroscopic 1,3,5'-'triazino- 2,4,6 trislu aminoethylene- ,B (tris N meth'ylmorpholine)] ammonium iodide, which when dried over phosphorous 'pentoxide in. a vacuum desiccator. gives a melting, point of about -'-135 C. Recrystallati'on from" dimethylformamide and ether. yields a purified product.

EXAMPLE X Preparation: of; 1,3,5=triazino-tris-2,4,6(aminotrimethyle ene)-tris-'y-diethylbenzyl ammonium chloride (6) 2,4,6 m'sw diethylaminotrimethyleneamine )r 1,3,5 triazine.-In a3-liter," 3 necked'fiask'equippd with a bulb reflux-condenser and sealed stirrer, a solution of 61.0 g. cyanuric'chloride in 600 ml. benzene isad'ded dropwise with stirring .to a solutionof 294 g. of gammadiethylaminopropylan'line in 600 ml. benzene under anhydrous conditions. The-resultingmixture is warmedto 75 80' CI and maintained under theseconditions until a test for ionic chlorine indicates substantially complete reaction. The mixture is. then concentrated by distillation,.and after cooling to room temperature, 600ml. ether and 450 ml.'.10%' aqueoussodium hydroxidevareadded tothe concentrate. to.a'separatory funneland the organic layeris extracted withlether. Theether extract is washedwithwsaturated sodiumchloridesolution, dried over anhydrous potassium carbonate and filtered. vAfter removal of the solvent by distillation,.the mixture is :vacuum. distilled, .first to separate the diethylaminopropylamine and then to yield about The resulting solution is transferred 128 .g. purified '2,4,6-tris(y-diethylaminotrimethyleneainine)-l,3,5-triazine, B. P. 250253 C. at, 0.2 to 0.3 mm. Hg. 1

(b) 1,3,5 triazino 2,4,6 tris (aminotrimethylendtris-y-diethylbenzyl ammonium chloride.A 23.3 g. portion of the product obtained as described in (a) is dissolved in 100 ml. acetone, added to a solution of 16.5 g. benzyl chloride in 100 ml. anhydrous acetone, and the mixture is allowed to remain at room temperature in a stoppered flask until an oil no longer separates from the solution. The supernatant liquor is then decanted and the oil is triturated with ether, then taken up in tertiary butanol at 30' C. Anhydrous ether is added to the tertiary butanol solution, and the resulting precipitate is separated to yield about 38 g. amorphous solid which, after vacuum drying over phosphorous pentoxide, melts at 110- 128 C. (indefinite). The purified l,3,5-triazino-2,4,6- tris(aminotrimethylene)-tris-'y-diethylbenzyl ammonium chloride is obtained by dissolving this product in chloroform, adding ether to precipitate the quaternary ammonium salt,- separating the salt by filtration, .then drying it in a vacuum oven for 48 hours at 70 C. to yield the purified product, M. P. 138 C. (dec.).

EXAMPLE XI Preparation of 1,3,5-triazino-2,4,6-tris(aminoethylene)- tris-dimethylbenzyl ammonium chloride (a) 2,4,6 tris dimethylaminoethylamino 1,3,5-t riazine.-In a3-liter, 3-necked flask equipped with a bulb reflux condenser and sealed stirrer, a solution of 93 g. cyanuric chloride in 800 ml. benzene is added dropwise with stirring to a solution of 352 g. dimethylaminoethylamine in 800 ml. benzene. The reaction mixture is then heated with a stirring at 60 C. until a test for ionic chlorine indicates substantially complete reaction. The mixture is then cooled, suction filtered, and the filter cake washed with benzene. The combined benzene extracts and washings are heated to remove the solvent. The crude residue is then taken up in a mixture of ether and benzene, washed first with aqueous sodium hydroxide solution, then with saturated sodium chloride solution and dried over anhydrous potassium carbonate. The residual solvent is removed by distillation to yield about 62 g. crude 2,4,6-tris-dimethylaminoethylamino-1,3,5-triazine which, on vacuum distillation, yields the purified product, B. P. 195-205 C. at 0.2 mm. Hg. (b) 1,3,5 triazino 2,4,6-zris(aminoethylene)-tris-a'imethylbenzyl ammonium chloride.A 24.0 g. portion of the product obtained as described in (a) is dissolved in a mixture of 200 ml. benzyl alcohol and 100 ml. anhydrous acetone, and added to a solution'of 28.0 g. benzyl chloride in 100 m1. anhydrous acetone. During the addition, the temperature rises to about 45 C. The clear solution obtained is concentrated by distillation and the resulting viscous liquid is titrated with ether, then filtered. The resulting solid material is dried in a vacuum desiccator over phosphorous pentoxide at 70-75 C. to yield about 44 g. l,3,5-triazino-2,4,6-tris(aminoethylene)- tris-dimethylbenzyl ammonium chloride.

EXAMPLE XII Preparation of 1,3,5-triazin0-2,4,6-tris(mercaptoethylene)-tris-diethylbenzylammonium chloride (a) 2,4,6-tris(fi-diethylaminoethylmarcapto)-1,3,5-triazine-To a suspension of 23 g. finely divided sodium in 500 ml. anhydrous benzene is added, dropwise with stirring, a solution of 133 g. B-diethylaminoethyl mercaptan in 500 ml. benzene. The temperature is maintained below 50 C. (by occasional cooling with ice water) andthe stirring is continued until the evolution of hydrogen ceases. A solution of 61.5 g. cyanuric chloride in 500 ml. anhydrous benzene is then added dropwise with stirring,

and the resulting mixture is heated for 5 hours at gentle reflux. After cooling, the reaction mixture is poured into one liter of water. Thebenzene layer is then separated, washed twice with 10% aqueous sodium chloride and dried over anhydrous potassium carbonate. The benzene is then removed by distillation and the residue is fractionally distilled under reduced pressure to yield the 2,4,6-tris(fi-diethylarninoethylmercapto)-1,3,5-triazine as a viscous oil.

(b) 1,3,5- triazino 2,4,6-trz's(mercaptoethylene)-trisa'iethylbenzylammonium chl0ride.A solution of 48.8 g. product obtained as described in (a) and 50 g. benzyl chloride in 250 ml. dry benzyl alcohol is allowed to remain at room temperature overnight. The unreacted benzyl chloride and benzyl alcohol are then separated from the reaction mixture by distillation under reduced pressure. The residual oil is triturated with anhydrous ethyl ether, then filtered to isolate the 1,3,5-triazino-2,4,-6.- tris (mercaptoethylene)-tris-diethylbenzylammonium chloride. The product may be recrystallized from ethylene dichloride, or from a mixture of ethanol and ethyl ether.

This invention may be variously otherwise embodied within the scope of the appended claims.

We claim:

1. Compounds of the general formula wherein R and R are each alkyl and together with the N atom to which they are joined form a saturated heterocyclic radical selected from the class consisting of piperi dino, morpholino and pyrrolidino; R" is a radical selected from the class consisting of alkyl and aralkyl; Y is a radical selected from the class consisting of O, S, NH, and N-lower alkyl; Z is selected from the class consisting of hydrogen and X is a pharmacologically acceptable anion; and n is an integer from 1 to 7, both inclusive.

,2. The 1,3,5 triazino 2,4,6-tris-(oxy-lower-alkylene)- tris-(benzyl di-lower-alkyl) ammonium salts.

3. The 1,3,5 triazino 2,4,6-tris-(oxy-lower-alkylene)- tris-(benzyl di-lower-alkyl) ammonium halides.

4. The 1,3,5 triazino 2,4,6-tris-oxyethylene-tris-(ben: zyl diethyl) ammonium salts. f p

5. The 1,3,5-triazino 2,4,6 tris-oxyethylene-tris(henzyl diethyl) ammonium halides.

6. The l,3,5-triazino-2,4,6-tris-(amino-lower alkylene)- tris-(benzyl di-loWer-alkyl) ammonium salts.

7. The 1,3,5-triazino-2,4,6-tris-(amino-lower-alkylene)- tris-(benzyl di-lower-alkyl) ammonium halides.

8. The process which comprises mixing cyanuric chloride, at an elevated temperature, with a di-lower-alkylamino-lower-alkanol, and reacting the. resulting product with an inorganic acid ester of benzyl alcohol to form the quaternary ammonium salt.

' 9. The process of claim 8 wherein the inorganic acid ester is benzyl halide. 1

10. The process which comprises mixing cyanuric chloride, at an elevated temperature, with a member of the group consisting of (1) an alcoholate of a tertiary amino alkanol, (2) a thioalcoholate of a tertiary amino alkanol and (3) a tertiary aminoalkylamine, wherein the tertiary amino radical in each instance is selected from the class consisting of dialkylamino, piperidino, morpholino and 9 10 pyrrolidino, then treating the resulting product with an piperidino, morpholino and pyrrolidino, and recovering inorganic acid ester to form the quaternary ammonium the tertiary amine-containing ether produced. salt. 12. The process of claim 11 wherein the resulting prod- 11. The process which comprises mixing cyanuric chlonot is treated with an inorganic acid ester to form the ride, at an elevated temperature, with an alcoholate of a 5 quaternary ammonium salt. tertiary amino alkanol, wherein the tertiary amino radical is selected from the class consisting of dialkylamino. No references cued- 

1. COMPOUNDS OF THE GENERAL FORMULA 